In rats with advanced malignant disease, the liver extracted circulati
ng glutamine at a ratio three times faster than the liver of control n
on-tumour-bearing animals. This augmented uptake occurred in spite of
a fall in circulating glutamine levels, implying an increase in hepato
cyte plasma membrane transport. Na+-dependent glutamine transport acti
vity (System N) was increased nearly two-fold in hepatocyte plasma mem
brane vesicles from tumour-bearing rats; this increase in System N act
ivity was proportional to tumour size and was due to an increase in ca
rrier V(max) with no change in carrier affinity. Measurement of System
N activity in isolated hepatocytes incubated with serum from tumour-b
earing rats demonstrated a significant increase in glutamine transport
compared with cells incubated with serum from control rats. These dat
a indicate that the liver of rats with advanced malignant disease disp
lays accelerated glutamine consumption. This increased uptake is due,
in part, to enhanced carrier-mediated transport activity, and is media
ted by a circulating factor(s) that is not present (or inactive) in no
n-tumour-bearing controls.